Mice of a variety of inbred strains are actively undergoing an immune response to endogenous leukemia viruses (MuLV). This is reflected by the presence of circulating antibodies, in the sera of normal mice, against the gp70 and p15(E) envelope proteins of MuLV. Immune response to MuLV is controlled by two major genetic factors: (1) genes that control the expression of endogenous MuLV determine the presentation of immunogen to the host; (2) genes in the IXth linkage group, mapping within H-2, determine the ability of the host to develop a secondary immune response to MuLV. Immunization of mice with leukemic cells induces an immune response to the viral envelope proteins gp70 and p15(E), as well as to two glycosylated forms of the gag gene product. Antibodies to these glycosylated polyproteins crossreact with the p30 protein of the viral core. The purpose of this research project is to investigate further the parameters of immune response to MuLV and leukemia-associated antigens. In the initial phase of this program we will perform a detailed analysis of the humoral and cellular components of natural immunity against leukemias. This analysis will be directed at determining the efficacy of this immune response in controlling the occurrence of spontaneous leukemias. Genetic crosses that segregate for immune response, production of infectious MuLV, and spontaneous leukemogenesis will be used to determine relationships between these phenomena. Subsequent studies will lead to the isolation of viral and cell-associated antigens for chemical analysis and production of nonspecific antisera. Purified antigens will then be used for immunization of mice to determine immunogenicity and potential protective effects against disease.